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| | Acetamide, N-[3-chloro-4-(4-methyl-1-piperazinyl)phenyl]-2-[4-(3,4-dihydro-5,7-dimethoxy-4-oxo-2-quinazolinyl)phenoxy]- Basic information |
| | Acetamide, N-[3-chloro-4-(4-methyl-1-piperazinyl)phenyl]-2-[4-(3,4-dihydro-5,7-dimethoxy-4-oxo-2-quinazolinyl)phenoxy]- Chemical Properties |
| density | 1.36±0.1 g/cm3(Predicted) | | storage temp. | Store at -20°C | | solubility | DMSO : 20 mg/mL (35.46 mM; ultrasonic and warming and adjust pH to 3 with HCl and heat to 60°C) | | pka | 12.10±0.70(Predicted) | | form | Solid | | color | White to off-white |
| | Acetamide, N-[3-chloro-4-(4-methyl-1-piperazinyl)phenyl]-2-[4-(3,4-dihydro-5,7-dimethoxy-4-oxo-2-quinazolinyl)phenoxy]- Usage And Synthesis |
| Uses | BRD4/CK2-IN-1 is the first highly effective and oral active dual-target inhibitor of BRD4/CK2 (bromodomain-containing protein 4/casein kinase 2), with IC50s of 180 nM and 230 nM for BRD4 and CK2, respectively. BRD4/CK2-IN-1 has strong anticancer activity without obvious toxicities. BRD4/CK2-IN-1 induces apoptosis and autophagy-associated cell death in triple-negative breast cancer (TNBC)[1] | | in vivo | BRD4/CK2-IN-1 (25 and 50 mg/kg; intragastric administration; daily for 19 days) inhibits tumor growth in TNBC xenograft models[1].
BRD4/CK2-IN-1 (25 and 50mg/kg; intragastric administration; daily for 19 days) shows weak toxicity measured by body weight loss in the MDA-MB-231 and MDA-MB-468 xenograft models[1].
Preliminary Assessment of Pharmacokinetics (PK) profile of BRD4/CK2-IN-1[1].
| Parameter | iv (1 mg/kg) | po (10 mg/kg) | | T1/2 (h) | 4.21±0.57 | 5.14±0.71 | | Cmax (ng/mL) | 237±11 | 206±6 | | AUC0-t (ng·h/mL) | 579±49 | 2079±130 | | AUC0-∞ (ng·h/mL) | 588±36 | 2090±146 | | VZ (L/kg) | 21.1±2.6 | | | CL ((mL/min)/kg) | 57.4±1.3 | | | F (%) | | 32.5 |
| Animal Model: | Female nude mice (BALB/c, 6-8 weeks, 20-22 g) bearing MDA-MB-231 cells[1] | | Dosage: | 25 and 50 mg/kg | | Administration: | Intragastric administration; daily for 19 days | | Result: | Had the most pronounced tumor growth inhibition (TGI) (63.8%) in the MDA-MB-231 xenograft tumor model at 50 mg/kg.
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| | IC 50 | BRD4: 180 nM (IC50); CK2: 230 nM (IC50) | | References | [1] Zhang J, et al. Discovery of Novel Dual-Target Inhibitor of Bromodomain-Containing Protein 4/Casein Kinase 2 Inducing Apoptosis and Autophagy-Associated Cell Death for Triple-Negative Breast Cancer Therapy. J Med Chem. 2021;64(24):18025-18053. DOI:10.1021/acs.jmedchem.1c01382 |
| | Acetamide, N-[3-chloro-4-(4-methyl-1-piperazinyl)phenyl]-2-[4-(3,4-dihydro-5,7-dimethoxy-4-oxo-2-quinazolinyl)phenoxy]- Preparation Products And Raw materials |
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